Tuberous sclerosis complex exhibits a new renal cystogenic mechanism.

Abstract

Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an intact Tsc gene that have been induced to exhibit Tsc-mutant disease phenotype. This mechanism appears to be different than that for ADPKD. The murine models described here closely resemble the human disease and both appear to be mTORC1 inhibitor responsive. The induction signaling driving cystogenesis may be mediated by extracellular vesicle trafficking.

• Authors: John J Bissler, Fahad Zadjali, Dave Bridges, Aristotelis Astrinidis, Sharon Barone, Ying Yao, JeAnna R Redd, Brian J Siroky, Yanqing Wang, Joel T Finley, Michael E Rusiniak, Heinz Baumann, Kamyar Zahedi, Kenneth W Gross, Manoocher Soleimani
• Journal: Physiological reports (Physiol Rep) Vol. 7 Issue 2 Pg. e13983 (01 2019) ISSN: 2051-817X [Electronic] United States
• PMID: 30675765 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Chemical References

• Tsc1 protein, mouse
• Tsc2 protein, mouse
• Tuberous Sclerosis Complex 1 Protein
• Tuberous Sclerosis Complex 2 Protein
• Mechanistic Target of Rapamycin Complex 1

Topics

• Animals
• Disease Models, Animal
• Extracellular Vesicles (genetics, metabolism, pathology)
• Female
• Kidney Diseases, Cystic (genetics, metabolism, pathology)
• Mechanistic Target of Rapamycin Complex 1 (metabolism)
• Mice
• Mice, Knockout
• Tuberous Sclerosis (genetics, metabolism, pathology)
• Tuberous Sclerosis Complex 1 Protein (genetics, metabolism)
• Tuberous Sclerosis Complex 2 Protein (genetics, metabolism)